acid-phosphatase and Colorectal-Neoplasms

Topics: Acid Phosphatase; alpha-Fetoproteins; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Colorectal Neoplasms; Humans; Male; Prostate-Specific Antigen

Colorectal cancer (CRC) is one of the leading cancers worldwide. Surgery is the main therapeutic modality for stage II CRC. However, the implementation of adjuvant chemotherapy remains controversial and is not universally applied so far. In this study, we found that the protein expression of lysosomal acid phosphatase 2 (ACP2) was increased in CRC and that stage II CRC patients with high ACP2 expression showed a poorer outcome than those with low ACP2 expression (p = 0.004). To investigate this discrepancy, we analyzed the relation between ACP2 expression and several clinical cofactors.Among patients who received chemotherapy, those with an high expression of ACP2 showed better survival in both stage II and III CRC than those with low ACP2 expression. In stage II CRC patients, univariate analysis showed ACP2 expression and T stage to be cofactors significantly associated with overall survival (ACP2: p = 0.006; T stage: p = 0.034). Multivariate Cox proportion hazard model analysis also revealed ACP2 to be an independent prognostic factor for overall survival (ACP2: p = 0.006; T stage: p = 0.041). Furthermore, ACP2-knockdown CRC cells showed an increase in chemoresistance to 5-FU treatment and increased proliferation marker in the ACP2 knockdown clone.Taken together, our results suggested that ACP2 is an unfavorable prognostic factor for stage II CRC and may serve as a potential chemotherapy-sensitive marker to help identify a subset of stage II and III CRC patients for whom chemotherapy would improve survival.Highlights1. To the best of our knowledge, the study is the first report to show ACP2 overexpression in human colorectal cancer (CRC) and its association with poor outcome in stage II CRC.2. Patients with stage II and III CRCs with high expression of ACP2 were more sensitive to chemotherapy than those with a low expression.3. ACP2 expression may serve as a marker for CRC patients receiving chemotherapy and help identify the subset of CRC patients who would benefit from chemotherapy.

Topics: Acid Phosphatase; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Blotting, Western; Cell Line, Tumor; Cell Movement; Cell Survival; Colorectal Neoplasms; Fluorouracil; HCT116 Cells; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Multivariate Analysis; Neoplasm Staging; Outcome Assessment, Health Care; Prognosis; Proportional Hazards Models; RNA Interference

Bone metastases develop in several malignancies (multiple myeloma, breast, prostate and lung carcinoma) and cause several complications. The aim of this study was to search for new biomarkers to use in monitoring of bone metastatic disease with the use of xMAP technology.. We assessed 62 oncological patients: 23 with no bone metastases, 28 with metastatic disease not having undergone therapy and 11 with metastatic disease treated by denosumab. Serum levels of dickkopf-related protein 1 (DKK1), growth differentiation factor-15 (GDF15), neuron-specific enolase (NSE), osteoprotegerin (OPG), osteonectin, periostin, tartrate-resistant acid phosphatase (TRAP5), tumor necrosis factor related weak inducer of apoptosis (TWEAK), chitinase-3-like protein 1 (YKL40), carboxy-terminal telopeptide (CTX) and procollagen type 1 N-terminal propeptide (PINP) were measured in each sample.. The following biomarkers were observed to have significantly higher levels in the groups of patients with metastases in comparison to metastasis-free patients: GDF15 (p<0.0001), osteonectin (p=0.0311), TRAP5 (p<0.0046), TWEAK (p<0.0343) and YKL40 (p<0.0034). The changes in DKK1, NSE, OPG and periostin were not significant.. We identified five new biomarkers: GDF15, osteonectin, TRAP5, TWEAK, and YKL40 as being promising markers for monitoring bone metastases.

Topics: Acid Phosphatase; Adipokines; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Chitinase-3-Like Protein 1; Colorectal Neoplasms; Cytokine TWEAK; Female; Growth Differentiation Factor 15; Humans; Isoenzymes; Lectins; Lung Neoplasms; Male; Middle Aged; Osteonectin; Pilot Projects; Prostatic Neoplasms; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factors

1alpha,25-dihydroxyvitamin D(3) and two synthetic analogs, 1alpha, 25-dihydroxy-16-ene-23-yne-vitamin D(3) (Ro 23-7553) and 1alpha, 25-dihydroxy-16-ene-24-oxo-vitamin D(3) (JK-1624-3), were tested for their ability to specifically inhibit growth and promote differentiation of human colon cancer cells in comparison with a series of 1beta-(hydroxymethyl) congeners of the natural hormone, such as 1beta-(hydroxymethyl)-3alpha,25(OH)(2)-16-ene,24-oxo-vitamin D(3) (JK-1624-2), 1beta-(hydroxymethyl)-3alpha, 25-dihydroxy-16-ene-26,27-dihomo vitamin D(3) (JK-1626-2), and 1beta-(hydroxymethyl)-3alpha,25-dihydroxy-22,24-diene-26,27- dihomo vitamin D(3) (MCW-EE). Western blot analysis revealed that reduction of cyclin D1 levels is a key mechanism by which the vitamin D compounds under investigation inhibit Caco-2 tumor cell growth. Both the 1alpha-hydroxy- as well as the 1beta-hydroxymethyl-type vitamin D compounds, which exhibit only low affinity for the vitamin D receptor, significantly reduced [(3)H]thymidine DNA labeling in confluent Caco-2 cell cultures. This suggests that high-affinity binding to the vitamin D receptor is not an absolute prerequisite for genomic action on tumor cell growth. Hybrid analogs JK-1624-2 and MCW-EE, although antimitotically active, were rather ineffective in promoting phenotypic differentiation of human colon cancer cells. However, because both compounds also do not promote osteoclast differentiation from hematopoetic bone marrow cells, they still could be used as antimitotic agents in cancer therapy, even at dose levels that, with other analogs, could cause hypercalcemia.

Topics: Acid Phosphatase; Animals; Antineoplastic Agents; Blotting, Western; Bone Marrow; Caco-2 Cells; Calcitriol; Cell Division; Colorectal Neoplasms; Dihydroxycholecalciferols; DNA; Humans; Mice; Thymidine; Vitamin D